MICROBIOLOGY

Immunology lec. 3

Lect. Dr. Dheyaa S.A. Al-Hissnawy

Third year

Inflammation1. Inflammation: local defensive response

resulted by damage to body tissue.

1.Causative agents: microbial infection

physical agents (heat, radiant agents,

electricity, and sharp objectives) chemical

agents (acids, basis, and gases).

2.Signs: redness pain heat swelling

3. (and sometimes) loss of function.

Inflammation3.Functions of inflammation:

To destroy the injurious agent, if possible,

and to remove it and its by-products from the

body.

If destruction is not possible, to limit the

effects on the body by confining or walling off

the injurious agent and it's by products.

To repair or replace tissue damaged by the

injurious agent and it's by products.

Inflammation4. Stages of infection:

A. Vasodilatation and increase permeability of blood vessels: this is caused by chemical released by cells of damaged tissue listed in table (3-1)

Chemical Produced by Function

1 Histamine mast cell basophilesplatelets Vasodilatation

2 KininsBy liver and present in blood

plasma

Vasodilatation, Chemotaxis for granulocytes

3Prostaglandi

nsCells of damaged area

Vasodilatation, help phagocytes move through capillary wall.

4 Leukotrienes

mast cell of (skin, respiratory system, blood vessels) basophiles

Increase permeability of blood vessels, help attack phagocytes to pathogen

5

Cytokines: IL-1, IL-6, IL-8, IL-12, and TNF-α

Macrophages (fig. 3-1) Vasodilatation, increase permeability of blood vessels, Chemotactic factors

Activates vascular endothelium,

activates lymphocytes,local tissue destruction,

increase access of effector cells

Local effectsActivates vascular

endothelium, and increase vascular permeability

which leads to increase entry of

IgG, complement and cells to tissue and increase fluid

drainage to lymph nods

Chemotactic factor recruits neutrophils,

basophile and T cells to site of

infection

Lymphocyte activation,

increase antibody

production

Activates NK cells induces the

differentiation of CD4 T cells into

TH1

Systemic effectsFever

Production of IL-6

Fever, Moblization of metabolite shoks

Fever, induce acute- phase protein

production

Activated macrophages secret a range of cytokines

InflammationB. Phagocyte migration and phagocytosis: PMNs and

monocytes leave the blood and migrate to sites of infection in a multistep process mediated through adhesive interactions that are regulated by macrophage-derived cytokines and chemokines.1. The first step (Rolling adhesion) involves the

binding of leukocytes to vascular endothelium through interactions between E-selectins on the endothelium and their carbohydrate ligands on the leukocyte sialyl-LewisX moiety (s-LeX)

Inflammation2. The Tight binding does, however, allow stronger interactions, which

occur as a result of the induction of intercellular adhesion molecules ICAM-1 on the endothelium and the activation of its receptors leukocyte functional antigens LFA-1 on the leukocyte by contact with a chemokine like IL-8and its receptor.

3. This binding allows the leukocyte to squeeze between the endothelial cells forming the wall of the blood vessel leading to diapedesis and migration toward the source of chemokines.

Blood stream →

Vascular endothelium

→

Tissue

→

Rolling adhesion Tight binding Diapedesis Migration

LFA-1

ICAM-1

IL-8 receptor

E-selectins

s-LeX

chemokineIL-8

Inflammation

4.The invading microbes were eliminated by

phagocytosis of PMNs other phagocytes start

establishes for adaptive immune response.

5.The pain is caused by

nerve damage

pressure of edema

irritation by toxins.

Inflammation3. Tissue repair: the process in which tissue replace dead or

damaged tissue.

1. Skin has a high capacity for regeneration, whereas, cardio

muscular does not.

2. Some microbes evade phagocytosis and cause chronic

inflammation like Mycobacterium tuberculosis, such away

lead to continuous production of cytokines and induce

fibroblast in the site of infection to synthesis collagen fiber

which leads to fibrosis.

Fever

Fever : abnormally high body temperature

1. The most causes of fever are bacteria, toxin, and viruses.

2. Bacterial endotoxin (LPS) bound to CD14 on macrophage. This then

triggers the membrane protein Toll Like Receptor 4 (TLR4) to

signal to the nucleus, activating the transcription factor, which in

turn activates genes involved in production cytokines IL-

1(endogenous pyrogen) and TNF-α

3. These cytokines cause the hypothalamus to release prostaglandin

that reset the hypothalamic thermostat at high temperature, thereby

causing fever.

Fever4. A high body temperature is caused by constriction of blood

vessels, increase rate of metabolism, and shivering.

5. Fever is considered defense against disease according to:

IL-1 helps to activate T-cells and so on adaptive immunity.

High body temperature intensifies the effect of antiviral

interferon.

Increase production of transferrins that decrease the iron

availability to microbes.

High body temperatures increase speed of body reactions and

help tissue repair.

Antimicrobial substancesAntimicrobial substances: Complement system.

Complement is a system of more than 30 plasma

proteins that activates a cascade of proteolytic

reactions on microbial surfaces but not on host

cells, coating these surfaces with fragments that

are recognized and bound by phagocytic

receptors on macrophages. The cascade of

reactions also releases small peptides that

contribute to inflammation and cytolysis (fig. 3-3).

ComplementComplement activation can

occur on three pathways

according to activation manner:

A. Classical pathway: this

pathway is initiated by an

antigen-antibody reaction.

The splitting of C3 into C3a

and C3b starts a cascade that

result in cytolysis,

inflammation, and

opsonization. (fig 3-4)

ComplementB. Alternative pathway: this

pathway is activated by contact

between certain complement

protein (C3 and factors B, D,

and P) and pathogen there are no

antibody involved. Once C3a

and C3b are formed they

participate in cytolysis,

inflammation, and opsonization.

(fig 3-5)

ComplementC. Lectin pathway: when the

plasma protein mannose-

binding lectin (MBL) binds to

mannose sugar on the surface of

microbes. MBL function as an

opsonin that enhance

phagocytosis and splitting of C3

into C3a and C3b starts a

cascade that result in cytolysis,

inflammation, and opsonization.

(fig 3-6)

Thank you for lesson